The effects of a nitrogen mustard on both the morphology and several synthetic capacities of embryonic chick skeletal muscle cells in monolayer culture have been examined. Concentrations of nitrogen mustard which profoundly inhibit deoxyribonucleic acid synthesis specifically do not inhibit the development of multinuclearity in the contractile "ribbons" which form rapidly in culture. Nitrogen mustard affects the nuclear morphology of "fibroblast-like" and multinuclear muscle cells differentially. The mononucleated cells in treated cultures exhibit extreme nuclear enlargement which distinguishes them from the multinuclear cells as well as from both types of cells in control cultures. The nuclei of the multinuclear cells which form after nitrogen mustard treatment, however, do give evidence of having been affected by the treatment. They exhibit somewhat less uniformity of size than similar cells in control cultures. Analogous differences were described by Bodenstein (3) between potentially proliferating cells and postmitotic differentiating cells, marked nuclear enlargement being characteristic of cells in the proliferative zone. The results are more compatible with the hypothesis that multinuclearity arises through successive cell fusion than through amitotic nuclear multiplication, since it is unlikely that any form of nuclear replication could occur in the absence of DNA synthesis.